A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study REPLY

Department of Ophthalmology, Feinberg School of Medicine, Northwestern University and the Chicago Center for Vision Research, Chicago, Illinois 60611, USA.
American Journal of Ophthalmology (Impact Factor: 3.87). 04/2011; 151(4):671-81. DOI: 10.1016/j.ajo.2010.09.026
Source: PubMed


To compare the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% in preserving visual function in low-pressure glaucoma.
Randomized, double-masked, multicenter clinical trial.
Exclusion criteria included untreated intraocular pressure (IOP) >21 mm Hg, visual field mean deviation worse than -16 decibels, or contraindications to study medications. Both eyes received twice-daily monotherapy randomized in blocks of 7 (4 brimonidine to 3 timolol). Standard automated perimetry and tonometry were performed at 4-month intervals. Main outcome measure was field progression in either eye, defined as the same 3 or more points with a negative slope ≥-1 dB/year at P<5%, on 3 consecutive tests, assessed by pointwise linear regression. Secondary outcome measures were progression based on glaucoma change probability maps (GCPM) of pattern deviation and the 3-omitting method for pointwise linear regression.
Ninety-nine patients were randomized to brimonidine and 79 to timolol. Mean (± SE) months of follow-up for all patients was 30.0 ± 2. Statistically fewer brimonidine-treated patients (9, 9.1%) had visual field progression by pointwise linear regression than timolol-treated patients (31, 39.2%, log-rank 12.4, P=.001). Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points. More brimonidine-treated (28, 28.3%) than timolol-treated (9, 11.4%) patients discontinued study participation because of drug-related adverse events (P=.008). Similar differences in progression were observed when analyzed by GCPM and the 3-omitting method.
Low-pressure glaucoma patients treated with brimonidine 0.2% who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5%.

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    • "y approved by the United States Food and Drug Administration for use in human patients with glaucoma ( Lee and McCluskey 2008 ) . A recent clinical trial of low - pressure human glaucoma patients demonstrated that brimonidine 0 . 2% prevented visual field loss in comparison to timolol 0 . 5% despite both agents decreasing IOP to a similar extent ( Krupin et al . 2011 ) . These results suggest that brimonidine 0 . 2% may have a neuroprotective effect in glaucoma in addition to decreasing IOP ( Pfeiffer et al . 2013 ) . While brimonidine ' s safety profile is excellent in rabbits , primates and man ( Arthur and Cantor 2011 ) , it significantly reduced heart rate and pupil size in Beagles with primary "
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    • "Patients were randomly assigned to receive monotherapy with either topical brimonidine tartrate (0.2%) or timolol maleate (0.5%), and the visual field progression was studied. Visual field loss was preserved in patients treated with brimonidine despite similar IOP-lowering effect by the two drugs [15]. These results are consistent with brimonidine's known neuroprotective properties of enhancing RGC survival and blocking axonal degeneration [17] [24]. "
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    • "Furthermore, we have recently demonstrated that the application of melatoninergic compounds reduces the IOP of rabbits with ocular hypertension induced by the Trendelenburg position (Martinez-Aguila et al., 2013). The neuroprotective action of brimonidine has been confirmed in experimental models of glaucoma and even in patients with low pressure glaucoma (Wheeler et al., 2003; Krupin et al., 2011; Pinar-Sueiro et al., 2011), and our results with a 2 -adrenergic receptor upregulation mediated mainly by 5-MCA-NAT seem to suggest a possible additional beneficial effect of this melatoninergic treatment. However, confirmation of 5-MCA- NAT neuroprotection and of its ocular hypotensive potentiating effect in glaucomatous animal models is necessary to increase confidence in the use of 5-MCA-NAT as a viable therapy for glaucoma. "
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